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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/307980/2012

EMEA/H/C/000128

EPAR summary for the public

Crixivan

indinavir

This is a summary of the European public assessment report (EPAR) for Crixivan. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Crixivan.

What is Crixivan?

Crixivan is a medicine that contains the active substance indinavir. It is available as capsules (200 and 400 mg).

What is Crixivan used for?

Crixivan is used in combination with other anti-HIV medicines to treat adults infected with human immunodeficiency virus type 1 (HIV 1), a virus that causes acquired immune deficiency syndrome (AIDS).

The medicine can only be obtained with a prescription.

How is Crixivan used?

Treatment with Crixivan should be given by doctors who have experience in the treatment of HIV infection. Crixivan must be used in combination with other antiviral medicines. The standard dose is 800 mg every eight hours. The capsules should be swallowed whole without food but with water one hour before or two hours after a meal. Alternatively, Crixivan may be given with a low-fat, light meal. Crixivan can also be taken at a dose of 400 mg twice a day if each dose is taken with 100 mg ritonavir (another antiviral medicine). The use of Crixivan with ritonavir is based on limited evidence. The dose of Crixivan will need to be adjusted in patients taking some other medicines or who have problems with their liver. To avoid the risk of developing kidney stones, patients should drink plenty of liquids (at least 1.5 litres every day for adults).

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© European Medicines Agency, 2012. Reproduction is authorised provided the source is acknowledged.

How does Crixivan work?

The active substance in Crixivan, indinavir, is a protease inhibitor. It blocks an enzyme called protease, which is involved in the reproduction of HIV. When the enzyme is blocked, the virus does not reproduce normally, slowing down the spread of infection. Crixivan, taken in combination with other antiviral medicines, reduces the amount of HIV in the blood and keeps it at a low level. Crixivan does not cure HIV infection or AIDS, but it may delay the damage to the immune system and the development of infections and diseases associated with AIDS. Ritonavir is another protease inhibitor that is used as a 'booster'. It slows down the rate at which indinavir is broken down, increasing the levels of indinavir in the blood. This allows a lower dose of indinavir to be used for the same antiviral effect.

How has Crixivan been studied?

Crixivan without ritonavir has been studied in three studies involving a total of 524 adults infected with HIV. The studies looked at Crixivan taken on its own or in combination with other antiviral medicines, and compared it with other antiviral medicines (zidovudine, didanosine and lamivudine). The main measure of effectiveness was the viral load (the level of HIV in the patient's blood) after 24 weeks of treatment.

The company also presented the results of four studies from the scientific literature that looked at the effects of taking Crixivan in combination with ritonavir, including 20 patients who had already been taking Crixivan without ritonavir and 123 patients who had not taken HIV treatment before.

What benefit has Crixivan shown during the studies?

Crixivan in combination with other antiviral medicines but without ritonavir was more effective than the comparator medicines. In one study, 90% of those taking Crixivan in combination with zidovudine and lamivudine had viral loads below 500 copies/ml after 24 weeks, compared with 43% of those taking Crixivan alone and none of those taking zidovudine and lamivudine without Crixivan.

The published studies showed that Crixivan boosted with ritonavir produced similar blood levels of indinavir to Crixivan taken without ritonavir. The combination was effective for up to two years.

What is the risk associated with Crixivan?

The most common side effects with Crixivan (seen in more than 1 patient in 10) are increases in mean corpuscular volume (large red blood cells), decreases in neutrophils (a type of white blood cell), headache, dizziness, nausea (feeling sick), vomiting, diarrhoea, dyspepsia (heartburn), isolated asymptomatic hyperbilirubinaemia (instances of high blood bilirubin levels that do not cause any symptoms), increased levels of liver enzymes (alanine and aspartate transaminases), rash, dry skin, haematuria (blood in the urine), proteinuria (protein in the urine), crystalluria (crystals in the urine), asthenia (weakness) or fatigue (tiredness), taste perversion (an altered sense of taste) and abdominal pain (stomach ache). For a more complete list of all side effects reported with Crixivan, see the package leaflet.

Crixivan should not be used in people who may be hypersensitive (allergic) to indinavir or any of the other ingredients. Crixivan must not be used in patients who are taking any of the following medicines:

•    medicines that are broken down in the same way as Crixivan and are harmful at high levels in the blood;

•    amiodarone (used to correct irregular heartbeat);

Crixivan

•    terfenadine, astemizole (commonly used to treat allergy symptoms - these medicines may be available without a prescription);

•    cisapride (used to treat certain stomach problems);

•    alprazolam, triazolam, midazolam taken by mouth (used to treat anxiety or difficulty sleeping);

•    pimozide (used to treat mental illness);

•    ergot derivatives (used to treat migraine headache);

•    simvastatin, lovastatin (used to lower cholesterol in the blood);

•    rifampicin (used to treat tuberculosis);

•    St John's wort (a herbal preparation used to treat depression).

Additional restrictions apply when Crixivan is taken with ritonavir. See the package leaflet provided with ritonavir for the full list.

As with other anti HIV medicines, patients taking Crixivan may also be at risk of lipodystrophy (changes in the distribution of body fat), osteonecrosis (death of bone tissue) or immune reactivation syndrome (symptoms of infection caused by the recovering immune system). Patients who have problems with their liver (including hepatitis B or C infection) may be at an elevated risk of liver damage when taking Crixivan.

Why has Crixivan been approved?

The CHMP decided that Crixivan's benefits are greater than its risks and recommended that it be given marketing authorisation.

Other information about Crixivan

The European Commission granted a marketing authorisation valid throughout the European Union for Crixivan on 4 October 1996.

The full EPAR for Crixivan can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European Public Assessment Reports. For more information about treatment with Crixivan, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 05-2012.

Crixivan

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